BackgroundNilotinib, which inhibits cellular Abelson tyrosine kinase, may be an effective treatment for patients with Parkinson's disease (PD). The purpose of this study is to evaluate the outcomes of different doses of nilotinib in patients with PD.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Clinical Trials from inception to 7 March 2022 to identify all randomized controlled trials (RCTs) of nilotinib reporting outcomes of interest in patients with PD. Outcomes included tolerability, efficacy, safety, and CSF biomarker levels. Review manager 5.4 software was used to analyze all data.ResultsThree RCTs with a total of 163 patients were included. No significant difference was found between 150 mg nilotinib or 300 mg nilotinib and placebo in terms of tolerability, adverse events, or HVA levels. 300 mg nilotinib showed significantly higher Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) scores [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01] and 3,4-dihydroxyphenylacetic acid (DOPAC) levels [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01], and lower α-synuclein levels [SMD = −2.16, 95%CI = (−3.38, −1.84), P < 0.00001] compared with placebo. And compared with 150 mg nilotinib, 300 mg nilotinib showed significantly lower α-synuclein levels [SMD = −1.16, 95%CI = (−1.70, −0.61), P < 0.0001].ConclusionsAlthough our study demonstrated favorable tolerability and safety of different doses of nilotinib, and improvement in part of CSF biomarker levels of 300 mg nilotinib, the poor efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic.

Objective To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). Methods We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022. Results A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events. Conclusion IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.

WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between longacting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.

Background: At present, the effect of aspirin in preventing dementia or mild cognitive impairment (MCI) is controversial. Clarifying their association is of interest for subsequent relevant clinical trials. Methods: Four databases (PubMed, Embase, Web of science, and the Cochrane library) were searched from inception to May 12, 2023 for randomized controlled trials (RCTs) that explored the effects between aspirin and dementia or MCI. Two reviewers independently extracted and analyzed data using Stata software. Discrepancy was resolved by a third reviewer. The primary outcomes were dementia and MCI. The secondary outcomes were cognitive decline and changes in cognitive scores. Results: Five RCTs with 46804 participants at randomization were included. For the primary outcomes, low certainty evidence showed that aspirin was not associated with dementia (OR=0.93, 95%CI (0.85, 1.03), P＞0.05, I2=0%) or MCI (OR=1.00, 95%CI (0.88, 1.14), P＞0.05, I2=3.3%). For the secondary outcomes, moderate certainty evidence showed that aspirin was not associated with cognitive decline (OR=1.02, 95%CI (0.93, 1.11), P＞0.05, I2=0%) and a change in global cognitive score (SMD=-0.01, 95%CI (-0.03, 0.02), P＞0.05, I2=0%). Low certainty evidence showed that aspirin was not associated with a change in verbal learning memory score (SMD=-0.04, 95%CI (-0.09, 0.01), P＞0.05; I2=72.5%). Conclusions: Low and moderate certainty evidence showed that aspirin was not associated with dementia, MCI, cognitive decline, or better cognitive scores. Future research may need to focus more on subtypes of dementia, mainly vascular dementia or other vascular neurocognitive diseases, and assess whether aspirin has long-term clinical benefits in a large sample of patients with dementia or MCI.

Objective We performed a meta-analysis to assess the efficacy and safety of T-DXd in the treatment of HER2-expressing solid tumours. Methods We systematically searched PubMed, Web of Science, Embase and the Cochrane Library and collected studies published before March 17, 2023, on T-DXd for HER2-expressing tumours for a meta-analysis. We performed a subgroup analysis based on the different cancer types and the doses used. Results There were 11 studies including 1349 HER2-expressing patients in this meta-analysis. The pooled ORR was 47.91%, and the pooled DCR was 87.01%. The mPFS and mOS combined were 9.63 and 10.71 months, respectively. The most common adverse reactions in grades 1–2 were decreased appetite (49.3%) and vomiting (43.0%). The netropemia (31.2%) and leukopenia (31.2%) were the most common grade 3 and higher adverse reactions. Subgroup analysis showed that breast cancer had the best ORR and DCR, with 66.96 and 96.52%, respectively. Conclusions Overall, the efficacy of T-DXd in treating HER2-expressing solid tumours is encouraging, especially breast and non-small cell lung cancers, and has an acceptable safety profile. However, concerns remain about potentially serious treatment adverse events (e.g. interstitial lung disease/pneumonia). More well-designed, large-scale randomized controlled trials are needed to demonstrate our study.

Objective To analyze the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients and provide reference for clinicians. Methods We used R software to conduct a meta-analysis of phase II/III randomized controlled trials (RCT) on PARP inhibitors for cancer treatment published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to July 29th, 2022. Results We included 32 RCTs with 10,654 participants for this meta-analysis. For total PARP inhibitors, the incidence and risk ratio of all-grade hypertension were 12% and 1.22 (95% CI: 0.91–1.65, P = 0.19, I2 = 81%), and the incidence and risk ratio of grade 3–4 hypertension were 4% and 1.24 (95% CI: 0.74–2.08, P = 0.42, I2 = 68%). Compared with the control group, the niraparib group, olaparib 800 mg/day group, and olaparib plus cediranib group increased the risk of any grade and grade 3–4 hypertension, while the veliparib group and rucaparib group did not increase the risk of any grade and grade 3–4 hypertension, and olaparib 200 mg-600 mg/day group (exclude olaparib plus cediranib regime) reduced the risk of any grade and grade 3–4 hypertension. Conclusion Olaparib 200-600 mg/day (excluding olaparib plus cediranib regimen) may be the most suitable PARP inhibitor for cancer patients with high risk of hypertension, followed by veliparib and rucaparib. Niraparib, olaparib 800 mg/day and olaparib combined with cediranib may increase the risk of developing hypertension in cancer patients, clinicians should strengthen the monitoring of blood pressure in cancer patients and give medication in severe cases.